FDA Approves Bysanti for Treatment of Bipolar 1 Disorder and Schizophrenia

The US Food and Drug Administration (FDA) has approved Vanda Pharmaceuticals’ Bysanti (milsaperidone) for treatment of acute bipolar disorder and schizophrenia.¹ Bysanti is a new chemical entity in the atypical antipsychotic class, providing a novel therapeutic option.

The New Drug Application (NDA) for Bysanti was submitted to the FDA in April 2025, backed by multiple clinical studies which assessed the efficacy and safety of the drug.² Previous studies include 2 trials in acute episodes of schizophrenia, 1 trial in bipolar 1 disorder with manic or mixed episodes, and 1 relapse prevention study in schizophrenia.³ Due to the nature of Bysanti as a metabolite of Fanapt (iloperidone), Vanda was able to submit data from iloperidone clinical studies as part of the review for milsaperidone. Studies found that milsaperidone rapidly converts to iloperidone, and it was shown to be bioequivalent at high and low doses.⁴ This pharmacokinetic bridging strategy may be of particular interest, as it leverages an established evidence base while potentially streamlining regulatory evaluation.

"The Bysanti approval marks a significant step forward, offering patients and providers a reliable new treatment grounded in extensive clinical heritage," commented Mihael H. Polymeropoulos, MD, President, chief executive officer and chairman of Vanda Pharmaceuticals. "Bysanti exemplifies a new era of accelerated innovation in drug development that can transform how we address unmet needs in behavioral health,” he added.¹

Previous clinical trials showed Fanapt significantly improved schizophrenia symptoms (measured by Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale), along with extending time to relapse or impending relapse.^5,6 In bipolar disorder, patients showed improvements in symptoms, as measured by the Young Mania Rating Scale.⁷

Bysanti is an active metabolite of Fanapt, an atypical antipsychotic. Fanapt is believed to interact with a multitude of neurotransmitter receptors, targeting 5-hydroxytryptamine receptor 2 and D2 dopamine receptors. Bysanti is considered part of the atypical antipsychotic class and shows strong affinity to the alpha-1 adrenergic receptors. Vanda, the company developing Bysanti, reported discovering milsaperidone as an active metabolite of Fanapt, a drug that was FDA approved in 2009 for schizophrenia and in 2024 for acute treatment of manic or mixed episodes in bipolar disorder.

John J. Miller, MD, editor in chief of Psychiatric Times, shared cautious optimism about the approval. “Unfortunately, there is a paucity of literature publicly available on milsaperidone at this time,” he said in an interview. “Two clinical adverse effects that can occur with iloperidone are orthostatic hypotension due to alpha₁ adrenergic receptor antagonism and QT interval prolongation. It will be interesting to see if these effects are diminished on milsaperidone.”

“According to reports, the different physical chemistry properties of milsaperidone are conducive to future development of Bysanti as a long-acting injectable formulation, which would be a favorable delivery system option,” Miller added.

A phase 3 study of Bysanti as an adjunct to treat major depressive disorder is also underway, with results expected by the end of 2026.⁸ Vanda noted that the unique in-class receptor binding profile of Bysanti, featuring strong alpha-adrenergic binding in excess of dopamine and serotonin receptor binding, “makes it suitable for further investigation in conditions that include symptoms of hostility, agitation, and hyperarousal.”¹

Bysanti is expected to be available in the US for schizophrenia and bipolar 1 disorder later in 2026.

References

1. Vanda Pharmaceuticals announces FDA approval of BYSANTI™ (milsaperidone) for the treatment of bipolar I disorder and schizophrenia - a new chemical entity opening new horizons in psychiatric innovation. Press release. February 20, 2026. Accessed February 20, 2026. https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-announces-fda-approval-of-bysanti-milsaperidone-for-the-treatment-of-bipolar-i-disorder-and-schizophrenia---a-new-chemical-entity-opening-new-horizons-in-psychiatric-innovation-302693941.html

2. Kuntz L. New NDA submitted: Bysanti to treat acute bipolar 1 and schizophrenia. Psychiatric Times. April 1, 2025. https://www.psychiatrictimes.com/view/new-nda-submitted-bysanti-to-treat-acute-bipolar-i-and-schizophrenia

3. Vanda announces Bysanti NDA filing; FDA decision expected in early 2026. Press release. May 5, 2025. Accessed February 18, 2026. https://www.prnewswire.com/news-releases/vanda-announces-bysanti-nda-filing-fda-decision-expected-in-early-2026-302445753.html

4. Kang J. Milsaperidone under review for bipolar 1 disorder and schizophrenia. Medical Professionals Reference. May 5, 2025. Accessed February 18, 2026. https://www.empr.com/news/milsaperidone-under-review-for-bipolar-i-disorder-and-schizophrenia/

5. Efficacy and safety of iloperidone compared with placebo and active control in subjects with acute schizophrenia. ClinicalTrials.gov. December 13, 2024. Accessed February 19, 2026. https://clinicaltrials.gov/study/NCT00254202?term=NCT00254202&rank=1#xd_co_f=ZDUwNWMyNTktOTU0ZS00NzdiLTg5OGItZDNkNzE4NTZhZGRj~

6. Relapse prevention study in patients with schizophrenia (REPRIEVE). ClinicalTrials.gov. July 17, 2023. Accessed February 19, 2026. https://clinicaltrials.gov/study/NCT01291511?term=NCT01291511&rank=1#xd_co_f=ZDUwNWMyNTktOTU0ZS00NzdiLTg5OGItZDNkNzE4NTZhZGRj~

7. Evaluation of efficacy and safety of iloperidone in the acute treatment of manic or mixed episodes associated with bipolar 1 disorder. ClinicalTrials.gov. April 18, 2024. Accessed February 19, 2026. https://clinicaltrials.gov/study/NCT04819776#xd_co_f=ZDFjMjAyZWYtZDJmNy00YTgzLWEyZjUtNGVkMGVlODI0MmRi~

8. Evaluation of efficacy and safety of milsaperidone as adjunctive therapy in patients with major depressive disorder. ClinicalTrials.gov. November 12, 2025. Accessed February 19, 2026. https://clinicaltrials.gov/study/NCT06830044?intr=Milsaperidone&rank=1#xd_co_f=ZDUwNWMyNTktOTU0ZS00NzdiLTg5OGItZDNkNzE4NTZhZGRj~